ITGAL

Summary

ITGAL (integrin subunit alpha L, HGNC:6148) is a protein-coding gene on chromosome 16p11.2, encoding Integrin alpha-L (P20701). Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4.

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3683 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 126 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6148
Approved symbol	ITGAL
Name	integrin subunit alpha L
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	HNA-5, LFA-1, LFA1A
Ensembl gene	ENSG00000005844
Ensembl biotype	protein_coding
OMIM	153370
Entrez	3683

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 9 protein_coding, 8 nonsense_mediated_decay, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000356798, ENST00000358164, ENST00000433423, ENST00000562020, ENST00000562652, ENST00000562857, ENST00000563615, ENST00000564632, ENST00000564935, ENST00000565348, ENST00000565864, ENST00000566149, ENST00000566267, ENST00000568012, ENST00000568926, ENST00000568987, ENST00000569725, ENST00000676652, ENST00000677830, ENST00000678203, ENST00000678574, ENST00000679323, ENST00000875722, ENST00000875723, ENST00000955585, ENST00000955586

RefSeq mRNA: 2 — MANE Select: NM_002209 NM_001114380, NM_002209

CCDS: CCDS32433, CCDS45461

Canonical transcript exons

ENST00000356798 — 31 exons

Exon	Start	End
ENSE00001609957	30505244	30505300
ENSE00001610939	30499338	30499489
ENSE00001611961	30499074	30499234
ENSE00001643987	30479331	30479461
ENSE00001673761	30519857	30519967
ENSE00001688272	30517649	30517705
ENSE00001694693	30496097	30496294
ENSE00001704204	30496436	30496566
ENSE00001718084	30479091	30479208
ENSE00001721322	30518624	30518719
ENSE00001734661	30517797	30517895
ENSE00001795073	30516973	30517086
ENSE00002307830	30472742	30472898
ENSE00002580604	30521492	30523185
ENSE00003462916	30475513	30475580
ENSE00003477213	30494212	30494363
ENSE00003486165	30510361	30510471
ENSE00003528363	30475306	30475400
ENSE00003537413	30505389	30505462
ENSE00003540077	30506715	30506856
ENSE00003555884	30489254	30489386
ENSE00003571454	30484113	30484263
ENSE00003573300	30483827	30483959
ENSE00003574497	30510881	30510960
ENSE00003578629	30494713	30494850
ENSE00003583479	30481439	30481584
ENSE00003588603	30474196	30474298
ENSE00003600314	30511050	30511136
ENSE00003637265	30504175	30504264
ENSE00003674333	30489082	30489155
ENSE00003689471	30513771	30513846

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 16.4271 / max 761.3797, expressed in 490 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153661	7.6500	406
153659	4.3926	330
153660	3.6585	315
153662	0.5382	179
153663	0.1490	65
153664	0.0387	16

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.52	gold quality
monocyte	CL:0000576	98.35	gold quality
leukocyte	CL:0000738	98.34	gold quality
mononuclear cell	CL:0000842	98.24	gold quality
blood	UBERON:0000178	97.39	gold quality
spleen	UBERON:0002106	97.20	gold quality
lymph node	UBERON:0000029	96.70	gold quality
bone marrow cell	CL:0002092	95.22	gold quality
vermiform appendix	UBERON:0001154	94.18	gold quality
caecum	UBERON:0001153	91.42	gold quality
thymus	UBERON:0002370	89.59	gold quality
bone marrow	UBERON:0002371	89.25	gold quality
upper lobe of left lung	UBERON:0008952	88.74	gold quality
colonic epithelium	UBERON:0000397	88.14	gold quality
tonsil	UBERON:0002372	87.91	gold quality
upper lobe of lung	UBERON:0008948	87.91	gold quality
right lobe of liver	UBERON:0001114	87.10	gold quality
pylorus	UBERON:0001166	86.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.10	gold quality
superficial temporal artery	UBERON:0001614	85.90	gold quality
right lung	UBERON:0002167	85.26	gold quality
gall bladder	UBERON:0002110	85.22	gold quality
rectum	UBERON:0001052	84.63	gold quality
small intestine	UBERON:0002108	84.37	gold quality
mucosa of transverse colon	UBERON:0004991	84.26	gold quality
trabecular bone tissue	UBERON:0002483	83.68	gold quality
liver	UBERON:0002107	82.87	gold quality
lung	UBERON:0002048	82.63	gold quality
right uterine tube	UBERON:0001302	82.38	gold quality
lower lobe of lung	UBERON:0008949	81.57	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	39.68
E-MTAB-6678	yes	13.36
E-MTAB-8498	yes	10.10
E-MTAB-9067	yes	5.24
E-GEOD-130148	yes	3.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPG, DNMT1, E2F1, RFX1, RUNX1, RUNX3, SPI1, STAT6

miRNA regulators (miRDB)

63 targeting ITGAL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-940	99.37	66.14	2064

Literature-anchored findings (GeneRIF, showing 40)

• Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1 (PMID:11792712)
• important role for the integrin LFA-1 and the microtubular cytoskeleton in the Ca(2)(+)-mediated activation of PYK2 in T-lymphocytes (PMID:11867690)
• regulation of LFA-1 activation and neutrophil arrest on intercellular adhesion molecule 1 in shear flow (PMID:11929876)
• cd11a may play an important role in pathogenic process(in COPD) (PMID:11953106)
• hypomethylation of regions flanking the ITGAL promoter may increase CD11a expression and may be one mechanism contributing to increased T cell gene expression with aging (PMID:12020947)
• Effect of DNA methylation and chromatin structure on ITGAL tissue-specific expression. (PMID:12036881)
• cagA+ Helicobacter pylori induced homotypic aggregation of macrophage-like cells by up-regulation and recruitment of intracellular adhesion molecule 1 to the cell surface and mediates the aggregation via LFA-1 (PMID:12117984)
• there are increased CD4+ cells in ulcerative colitis and Crohn’s disease and there is enhanced expression of CD11a by this T-cell subset (PMID:12139949)
• results indicated that the constitutive CD11a expression in the myeloid lineage is implicated in oxidative stress occurring spontaneously (PMID:12163056)
• LFA-1 integrin activation by chemokines requires cholesterol (PMID:12163503)
• study demonstrates a role for the LFA-1 interaction with ICAM-1 in the lysis of bladder tumor cells by (BCG)-activated killer (BAK) and lymphokine-activated killer (LAK) cells (PMID:12202941)
• Porphyromonas gingivalis fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. (PMID:12207338)
• Increased expression in Mycobacterium tuberculosis-infected human macrophages exhibiting enhanced cellular adhesion (PMID:12368450)
• Adhesion of dendritic cells derived from CD34+ progenitors to resting human dermal microvascular endothelial cells is down-regulated upon maturation and partially depends on CD11a-CD18, CD11b-CD18 and CD36. (PMID:12516552)
• Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse. (PMID:12616499)
• ICAM-4 binds to the I domain of this integrin. (PMID:12694184)
• LFA-1 and TCR have essential roles in encounters of T cells with antigen-presenting cells and immunological synapse (IS) formation (PMID:12815062)
• A major cause of the poor cytotoxic activity of IL-7-differentiated cells is their low expression of LFA-1, an important marker for the development of competent natural killer (NK) cells following bone marrow transplantation. (PMID:12847234)
• RUNX3/AML-2 binding to the CD11a promoter correlates with increased RUNX3/AML-2 protein levels and enhanced CD11a/CD18 cell surface expression (PMID:12855590)
• CD226 is involved in LFA-1-mediated costimulatory signals for triggering naive T cell differentiation and proliferation. (PMID:14676297)
• TNF-alpha acts as a potent stimulator of Actinobacillus actinomycetemcomitans leukotoxin-induced HL-60 cell apoptosis via TNF receptor 1-mediated upregulation of LFA-1 expression. (PMID:14688105)
• Increased expression or CD11A may affect the development of initial atherosclerotic coronary stenosis, but not re-stenosis. (PMID:14695458)
• integrin LFA-1 binds to the plasma membrane phosphoprotein RanBPM and is coupled to integrins with intracellular signaling pathways (PMID:14722085)
• results identify novel, specific functional consequence of LFA-1-mediated cytolytic activity in perforin-containing human NK subsets (PMID:15113754)
• The ICAM-1/LFA-1 association was a more efficient transmission factor for HIV-1 bearing ICAM-1 than combined gp120/DC-SIGN & ICAM-3/DC-SIGN. The involvement of virus-bound ICAM-1 & LFA-1 in virus binding & carriage was confirmed in human lymphoid tissues. (PMID:15208262)
• LFA-1 to ICAM-1 adhesion is initiated by the formation of a single bond with approximately 0.3 s(-1) dissociation rate, and attachment is subsequently strengthened by the formation of additional bonds during the next 10 s. (PMID:15240749)
• Usinsg monoclonal antibodies to LFA-1alpha on monocytic cells, found that cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment. (PMID:15308572)
• In contrast to T cells, in which even adhesion through LFA-1 is dependent on signals from other receptors, natural killer (NK) cells receive early activation signals directly through LFA-1. (PMID:15356110)
• The LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands. (PMID:15611342)
• Acute myeloid leukemia cells might adhere to and get through vascular endothelium by CD49d/VCAM-1 and CD11a/ICAM-1 adhesion mechanism. (PMID:15622747)
• CD226 molecules play an important role in maturation of the megakaryocytes in combination with LFA-1 (PMID:15693793)
• chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion (PMID:15834409)
• LFA-1 delivers a distinct signal essential for directing released cytolytic granules to the surface of antigen-bearing target cells to mediate the effective destruction of these cells by cytotoxic T lymphocytes. (PMID:15851656)
• the hybrid domain of integrin alphaL beta2 has different requirements of affinity states for ICAM-1 and ICAM-3 binding (PMID:15958383)
• Talin is essential for the stability and formation of the LFA-1 zone. Disruption of the talin-integrin link leads to loss of zone integrity and a substantial decrease in speed of migration on ICAM-1. (PMID:15983060)
• LFA-1 activation state and cluster formation mediate the initial steps of HIV-1 binding and entry inside activated CD4+ T lymphocytes. (PMID:16002691)
• In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c was increased, and upon PMN activation in DVT subjects CD11b, CD11c and CD18 increased, while CD11a expression did not show any change (PMID:16037628)
• lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the canal of Hering in biliary cirrhosis (PMID:16038038)
• biophysical analysis of how lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow (PMID:16100282)
• In primary neutrophils unengaged LFA-1 is internalized and rapidly recycled upon chemoattractant stimulation via a clathrin-independent, cholesterol-sensitive pathway. (PMID:16207819)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Itgal	ENSMUSG00000030830
rattus_norvegicus	Itgal	ENSRNOG00000017980
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	mew	FBGN0004456
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
caenorhabditis_elegans		WBGENE00002081
caenorhabditis_elegans		WBGENE00003929

Paralogs (17): ITGA3 (ENSG00000005884), ITGA2B (ENSG00000005961), ITGA8 (ENSG00000077943), ITGAE (ENSG00000083457), ITGA6 (ENSG00000091409), ITGA4 (ENSG00000115232), ITGA7 (ENSG00000135424), ITGA11 (ENSG00000137809), ITGAV (ENSG00000138448), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-L — P20701 (reviewed: P20701)

Alternative names: CD11 antigen-like family member A, Leukocyte adhesion glycoprotein LFA-1 alpha chain, Leukocyte function-associated molecule 1 alpha chain

All UniProt accessions (12): P20701, A0A7I2V498, A0A7I2V4B0, A0A7I2V582, A0A7I2V5G1, B4DQ77, B4E021, H3BNL5, H3BS37, H3BUT3, I3L1D1, I3L468

UniProt curated annotations — full annotation on UniProt →

Function. Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is a receptor for F11R. Integrin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Acts as a platform at the immunological synapse to translate TCR engagement and density of the ITGAL ligand ICAM1 into graded adhesion. Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. Integrins ITGAL:ITGB2 functions as a receptor of the neuron-specific adhesion molecule ICAM5 ensuring neuron cell-leukocyte adhesion. Integrin ITGAL/ITGB2 that functions as a signaling receptor of ICAM2, ensuring leukocyte cell-cell adhesion on resting cells.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The ITGAL alpha subunit associates with the ITGB2 beta subunit. Interacts with THBD. Interacts with CD226. (Microbial infection) Interacts with SARS-CoV Orf7a protein.

Subcellular location. Cell membrane. Membrane raft.

Tissue specificity. Leukocytes.

Post-translational modifications. In resting T-cells, up to 40% of surface ITGAL is constitutively phosphorylated. Phosphorylation causes conformational changes needed for ligand binding and is necessary for activation by some physiological agents.

Domain organisation. The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. The I-domain is necessary and sufficient for interaction with ICAM1 and F11R.

Similarity. Belongs to the integrin alpha chain family.

Isoforms (3)

UniProt ID	Names	Canonical?
P20701-1	1	yes
P20701-2	2
P20701-3	3

RefSeq proteins (2): NP_001107852, NP_002200* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000413	Integrin_alpha	Family
IPR002035	VWF_A	Domain
IPR013517	FG-GAP	Repeat
IPR013519	Int_alpha_beta-p	Repeat
IPR013649	Integrin_alpha_Ig-like_1	Domain
IPR018184	Integrin_alpha_C_CS	Conserved_site
IPR028994	Integrin_alpha_N	Homologous_superfamily
IPR032695	Integrin_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR048285	Integrin_alpha_Ig-like_2	Domain

Pfam: PF00092, PF00357, PF01839, PF08441, PF20805

UniProt features (134 total): strand 40, helix 22, binding site 17, glycosylation site 12, disulfide bond 9, turn 8, repeat 7, sequence variant 4, splice variant 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, transmembrane region 1, modified residue 1, mutagenesis site 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

41 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1MJN	X-RAY DIFFRACTION	1.3
2ICA	X-RAY DIFFRACTION	1.56
3F78	X-RAY DIFFRACTION	1.6
1T0P	X-RAY DIFFRACTION	1.66
3F74	X-RAY DIFFRACTION	1.7
2O7N	X-RAY DIFFRACTION	1.75
1LFA	X-RAY DIFFRACTION	1.8
1XUO	X-RAY DIFFRACTION	1.8
3BQN	X-RAY DIFFRACTION	1.8
4IXD	X-RAY DIFFRACTION	1.8
7KC3	X-RAY DIFFRACTION	1.8
3M6F	X-RAY DIFFRACTION	1.85
7KC6	X-RAY DIFFRACTION	1.85
7KC5	X-RAY DIFFRACTION	1.86
3BQM	X-RAY DIFFRACTION	1.95
1MQ9	X-RAY DIFFRACTION	2
1ZON	X-RAY DIFFRACTION	2
1ZOP	X-RAY DIFFRACTION	2
3E2M	X-RAY DIFFRACTION	2
6BXJ	X-RAY DIFFRACTION	2.09
3BN3	X-RAY DIFFRACTION	2.1
1XDG	X-RAY DIFFRACTION	2.1
5E6S	X-RAY DIFFRACTION	2.15
1XDD	X-RAY DIFFRACTION	2.2
3HI6	X-RAY DIFFRACTION	2.3
6BXB	X-RAY DIFFRACTION	2.39
1RD4	X-RAY DIFFRACTION	2.4
1MQA	X-RAY DIFFRACTION	2.5
5E6U	X-RAY DIFFRACTION	2.5
1CQP	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20701-F1	82.77	0.42

Antibody-complex structures (SAbDab): 3 — 3EOA, 3EOB, 3HI6

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (17): 164; 166; 231; 264; 468; 470; 472; 474; 476; 530; 532; 534 …

Post-translational modifications (1): 1165

Disulfide bonds (9): 73–80, 111–129, 119–150, 636–717, 653–707, 771–777, 845–861, 998–1013, 1021–1052

Glycosylation sites (12): 65, 89, 188, 649, 670, 726, 730, 862, 885, 897, 1060, 1071

Mutagenesis-validated functional residues (1):

Position	Phenotype
1165	abolishes phosphorylation and mem-83-activated t-cell adhesion to icam1. abolishes integrin alpha-l/beta-2 activation by

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-8949275	RUNX3 Regulates Immune Response and Cell Migration
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-1474244	Extracellular matrix organization
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3

MSigDB gene sets: 357 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GNF2_CASP8, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, KYNG_DNA_DAMAGE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GNF2_ZAP70

GO Biological Process (13): T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291), phagocytosis (GO:0006909), inflammatory response (GO:0006954), cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), leukocyte cell-cell adhesion (GO:0007159), cell-matrix adhesion (GO:0007160), signal transduction (GO:0007165), integrin-mediated signaling pathway (GO:0007229), memory T cell extravasation (GO:0035683), receptor clustering (GO:0043113), cell-cell adhesion (GO:0098609), T cell activation (GO:0042110)

GO Molecular Function (6): ICAM-3 receptor activity (GO:0030369), signaling receptor activity (GO:0038023), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), integrin complex (GO:0008305), cell surface (GO:0009986), membrane (GO:0016020), integrin alphaL-beta2 complex (GO:0034687), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), secretory granule membrane (GO:0030667)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	1
Hemostasis	1
Extracellular matrix organization	1
Innate Immune System	1
Transcriptional regulation by RUNX3	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cell-cell adhesion	2
binding	2
cellular anatomical structure	2
T cell activation involved in immune response	1
endocytosis	1
defense response	1
cell-substrate adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
T cell extravasation	1
plasma membrane	1
protein localization to membrane	1
cell adhesion	1
lymphocyte activation	1
transmembrane signaling receptor activity	1
molecular transducer activity	1
cation binding	1
protein binding	1
membrane	1
cell periphery	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1
integrin complex	1
secretory granule membrane	1
specific granule	1
extracellular vesicle	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

2406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGAL	ITGB2	P05107	999
ITGAL	ICAM1	P05362	997
ITGAL	ICAM2	P13598	994
ITGAL	VCAM1	P19320	992
ITGAL	ICAM3	P32942	987
ITGAL	F11R	Q9Y624	960
ITGAL	ITGAM	P11215	930
ITGAL	CD58	P19256	903
ITGAL	CD2	P06729	890
ITGAL	ICAM5	Q9UMF0	875
ITGAL	SELE	P16111	857
ITGAL	SELL	P14151	850
ITGAL	ITGB1	P05556	841
ITGAL	AOC3	Q16853	837
ITGAL	CD4	P01730	816

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ITGAL	ICAM1	psi-mi:“MI:0407”(direct interaction)	0.730
ICAM1	ITGAL	psi-mi:“MI:0407”(direct interaction)	0.730
ITGAL	PTPRC	psi-mi:“MI:0915”(physical association)	0.510
PTPRC	ITGAL	psi-mi:“MI:0915”(physical association)	0.510
ITGAL		psi-mi:“MI:0915”(physical association)	0.510
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
ITGAL	ICAM3	psi-mi:“MI:0407”(direct interaction)	0.440
	ITGAL	psi-mi:“MI:0407”(direct interaction)	0.440
ICAM5	ITGAL	psi-mi:“MI:0407”(direct interaction)	0.440
ITGAL	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
RANBP9	ITGAL	psi-mi:“MI:0915”(physical association)	0.400
ITGAL	Rassf5	psi-mi:“MI:0915”(physical association)	0.400
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
VHL	ITGAL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): SHARPIN (Affinity Capture-Western), ITGAL (Reconstituted Complex), ITGAL (Far Western), SHARPIN (Protein-peptide), ITGAL (Reconstituted Complex), SHARPIN (Protein-peptide), SHARPIN (Far Western), SHARPIN (Affinity Capture-Western), PTPRC (Two-hybrid), PTPRC (Reconstituted Complex), PTPRC (Affinity Capture-Western), ITGAL (FRET), ITGAL (Reconstituted Complex), ITGAL (Affinity Capture-Western), HNRNPU (Proximity Label-MS)

ESM2 similar proteins: A0EQL2, A2AJ76, A2AJA7, A6H8M9, A8T650, A8T682, A8T688, A8T6A6, D3ZLH5, F1QVU0, O08628, O75173, O88839, P04278, P08514, P08689, P0DV84, P15196, P20701, P29376, P32970, P38570, P60882, P80012, P97497, P97793, Q13444, Q15113, Q5RFQ8, Q5TM20, Q61398, Q63191, Q6UXC1, Q7Z304, Q7Z442, Q7Z7M0, Q8BNJ2, Q8CG85, Q8K1S7, Q8NBP7

Diamond homologs: A2AX52, A6H584, A6NMZ7, A6QLN9, A8TX70, E7FF10, O00339, O08746, O42401, O75578, O89029, P05099, P05555, P11215, P12111, P15989, P20701, P20702, P34576, P51942, P61625, Q02388, Q13349, Q21281, Q21540, Q28902, Q3V0T4, Q63870, Q642A6, Q6PCB0, Q6UXI7, Q8C6K9, Q8NFW1, Q8R2Z5, Q90615, Q91145, Q923P0, Q95LI2, Q96P44, Q9P218

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PTPRG	“down-regulates activity”	ITGAL
JAK2	“up-regulates activity”	ITGAL	phosphorylation
SRC	“down-regulates activity”	ITGAL	phosphorylation
ITGAL	up-regulates	ICAM1	binding
SELE	up-regulates	ITGAL
ITGAL	“up-regulates activity”	AKAP9	binding
ITGAL	“form complex”	“AL/b2 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	12
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

4070 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30474074:G:GT	donor_gain	1.0000
16:30474074:G:T	donor_gain	1.0000
16:30474082:GG:G	donor_gain	1.0000
16:30474083:GG:G	donor_gain	1.0000
16:30479085:CTTTA:C	acceptor_loss	1.0000
16:30479086:TTTAG:T	acceptor_loss	1.0000
16:30479087:TTA:T	acceptor_loss	1.0000
16:30479088:TAGGC:T	acceptor_loss	1.0000
16:30479089:AGGC:A	acceptor_loss	1.0000
16:30479090:GGCCT:G	acceptor_gain	1.0000
16:30479329:A:AG	acceptor_gain	1.0000
16:30479330:G:GG	acceptor_gain	1.0000
16:30479330:GA:G	acceptor_gain	1.0000
16:30479330:GAAT:G	acceptor_gain	1.0000
16:30481436:TAGTT:T	acceptor_loss	1.0000
16:30481437:A:AG	acceptor_gain	1.0000
16:30481437:AGTTT:A	acceptor_gain	1.0000
16:30481438:G:GC	acceptor_gain	1.0000
16:30481438:GT:G	acceptor_gain	1.0000
16:30481438:GTT:G	acceptor_gain	1.0000
16:30481438:GTTT:G	acceptor_gain	1.0000
16:30481438:GTTTG:G	acceptor_gain	1.0000
16:30481580:GTCGC:G	donor_gain	1.0000
16:30481583:GC:G	donor_gain	1.0000
16:30481585:G:GG	donor_gain	1.0000
16:30483818:T:TA	acceptor_gain	1.0000
16:30483825:A:AC	acceptor_loss	1.0000
16:30483825:A:AG	acceptor_gain	1.0000
16:30483826:G:GT	acceptor_gain	1.0000
16:30483826:GGAC:G	acceptor_gain	1.0000

AlphaMissense

7685 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30481454:T:C	F198L	0.998
16:30481456:T:A	F198L	0.998
16:30481456:T:G	F198L	0.998
16:30481442:G:C	A194P	0.995
16:30481446:C:A	A195D	0.995
16:30483880:T:C	L259P	0.994
16:30479118:T:A	C119S	0.993
16:30479119:G:C	C119S	0.993
16:30479355:T:C	L157P	0.993
16:30479361:T:C	F159S	0.992
16:30479370:A:T	D162V	0.992
16:30479417:T:C	F178L	0.992
16:30479419:C:A	F178L	0.992
16:30479419:C:G	F178L	0.992
16:30481439:T:C	F193L	0.992
16:30481441:T:A	F193L	0.992
16:30481441:T:G	F193L	0.992
16:30481445:G:C	A195P	0.992
16:30481478:T:C	F206L	0.992
16:30481480:T:A	F206L	0.992
16:30481480:T:G	F206L	0.992
16:30505396:T:G	F767C	0.991
16:30518648:A:C	S1053R	0.991
16:30518650:C:A	S1053R	0.991
16:30518650:C:G	S1053R	0.991
16:30479371:T:A	D162E	0.990
16:30479371:T:G	D162E	0.990
16:30479381:A:C	S166R	0.990
16:30479383:C:A	S166R	0.990
16:30479383:C:G	S166R	0.990

dbSNP variants (sampled 300 via entrez): RS1000015257 (16:30479537 T>A,C), RS1000136272 (16:30508510 A>G), RS1000167609 (16:30483628 G>C), RS1000215271 (16:30472385 T>C), RS1000217833 (16:30519160 T>C), RS1000229394 (16:30479884 T>G), RS1000309561 (16:30522122 C>T), RS1000469275 (16:30497233 C>A), RS1000590607 (16:30503841 G>A), RS1000606255 (16:30504814 C>G,T), RS1000732159 (16:30512390 C>A), RS1000814274 (16:30498071 G>A), RS1000883827 (16:30510010 G>C), RS1000916717 (16:30491472 A>G,T), RS1000938626 (16:30517328 C>T)

Disease associations

OMIM: gene MIM:153370 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001728_14	Ulcerative colitis	6.000000e-10
GCST002361_28	Smooth-surface caries	2.000000e-07
GCST004133_32	Ulcerative colitis	1.000000e-06
GCST004610_146	White blood cell count	6.000000e-27
GCST004626_135	Myeloid white cell count	5.000000e-10
GCST004627_160	Lymphocyte count	1.000000e-59
GCST004632_47	Lymphocyte percentage of white cells	2.000000e-17
GCST004633_37	Neutrophil percentage of white cells	1.000000e-11
GCST005537_106	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-14
GCST90002388_166	Lymphocyte count	4.000000e-130
GCST90002389_308	Lymphocyte percentage of white cells	3.000000e-34
GCST90002398_296	Neutrophil count	8.000000e-20
GCST90002399_264	Neutrophil percentage of white cells	3.000000e-14
GCST90002407_554	White blood cell count	3.000000e-67

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1803 (SINGLE PROTEIN), CHEMBL2096661 (PROTEIN COMPLEX), CHEMBL2364172 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,540 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL503	LOVASTATIN	4	92,462
CHEMBL2048028	LIFITEGRAST	4	1,078

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2230433	ITGAL		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Integrins

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
efalizumab	Binding	11.4	pKd
BI-1950	Binding	8.05	pKd
BIRT 377	Binding	7.59	pKd

Binding affinities (BindingDB)

12 measured of 14 human assays (14 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(E)-3-(4-(3-(8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)phenylthio)-2,3-bis(trifluoromethyl)phenyl)-1-morpholinoprop-2-en-1-one	IC50	0.94 nM
CHEMBL3298195	IC50	16 nM
CHEMBL3298198	IC50	22 nM
CHEMBL3298197	IC50	23 nM
CHEMBL3298661	IC50	28 nM
CHEMBL3298411	IC50	37 nM
CHEMBL3298660	IC50	65 nM
CHEMBL3297752	IC50	100 nM
CHEMBL3298196	IC50	117 nM
CHEMBL3298406	IC50	180 nM
CHEMBL3298409	IC50	488 nM
CHEMBL3298408	IC50	7900 nM

ChEMBL bioactivities

643 potent at pChembl≥5 of 698 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL336789
9.46	IC50	0.35	nM	CHEMBL488318
9.41	IC50	0.39	nM	CHEMBL4794300
9.40	IC50	0.4	nM	CHEMBL452882
9.30	IC50	0.5	nM	CHEMBL472841
9.30	IC50	0.5	nM	CHEMBL520731
9.30	IC50	0.5	nM	CHEMBL337562
9.22	IC50	0.6	nM	CHEMBL502756
9.08	IC50	0.84	nM	CHEMBL88478
9.05	IC50	0.9	nM	CHEMBL485857
9.03	IC50	0.94	nM	CHEMBL444773
8.92	IC50	1.2	nM	CHEMBL1644132
8.85	IC50	1.4	nM	CHEMBL450871
8.85	IC50	1.4	nM	CHEMBL491402
8.85	IC50	1.4	nM	CHEMBL521080
8.85	IC50	1.4	nM	CHEMBL1221918
8.77	IC50	1.7	nM	CHEMBL478464
8.74	IC50	1.8	nM	CHEMBL526564
8.74	IC50	1.8	nM	CHEMBL1094128
8.74	IC50	1.8	nM	CHEMBL1098727
8.70	IC50	2	nM	CHEMBL2048036
8.70	IC50	2	nM	CHEMBL521708
8.70	IC50	2	nM	CHEMBL139349
8.68	IC50	2.1	nM	CHEMBL496945
8.62	IC50	2.4	nM	CHEMBL515393
8.60	IC50	2.5	nM	CHEMBL497978
8.60	IC50	2.5	nM	CHEMBL487705
8.60	IC50	2.5	nM	CHEMBL1098726
8.52	IC50	3	nM	CHEMBL2048025
8.52	IC50	3	nM	CHEMBL262911
8.52	IC50	3	nM	CHEMBL502789
8.52	IC50	3	nM	BI 1950
8.52	IC50	3	nM	CHEMBL337562
8.49	IC50	3.2	nM	CHEMBL500859
8.47	IC50	3.4	nM	CHEMBL446300
8.47	IC50	3.4	nM	CHEMBL443467
8.44	IC50	3.6	nM	CHEMBL1094115
8.43	IC50	3.7	nM	CHEMBL524347
8.41	IC50	3.9	nM	CHEMBL495906
8.40	IC50	4	nM	CHEMBL2048402
8.40	IC50	4	nM	CHEMBL502512
8.40	IC50	4	nM	CHEMBL1094127
8.40	IC50	4	nM	CHEMBL139068
8.40	IC50	4	nM	CHEMBL138185
8.36	IC50	4.4	nM	CHEMBL479061
8.36	IC50	4.4	nM	CHEMBL1098437
8.32	IC50	4.8	nM	CHEMBL1095138
8.30	IC50	5	nM	CHEMBL1096088
8.30	IC50	5	nM	CHEMBL1222290
8.30	IC50	5	nM	CHEMBL1222288

PubChem BioAssay actives

639 with measured affinity, of 966 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[(E)-3-[4-(2-methoxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94614: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(2-8)	ic50	0.0001	uM
(E)-1-morpholin-4-yl-3-[4-[3-[(1-propan-2-ylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0003	uM
2-[1-[(4-aminophenyl)methylcarbamoyl]-4-oxoazetidin-2-yl]acetic acid;2,2,2-trifluoroacetic acid	1686207: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay	ic50	0.0004	uM
4-[[2-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]methyl]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0004	uM
1-[(E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94612: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(0.03-0.5)	ic50	0.0005	uM
4-[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylanilino]cyclohexane-1-carboxylic acid	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0005	uM
(E)-3-[4-[3-[(1-methylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0005	uM
(2S)-1-[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-4-methyl-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]pentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxylic acid	1686207: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay	ic50	0.0008	uM
(E)-1-morpholin-4-yl-3-[4-[3-[(1-propylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0009	uM
(E)-3-[4-[3-[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0009	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(5-methylsulfonylfuran-2-yl)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0012	uM
(2S)-2-[[2,6-dichloro-4-[3-hydroxy-3-(3-hydroxyphenyl)propyl]benzoyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid	501409: Inhibition of LFA1 by ELISA	ic50	0.0014	uM
4-[[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylanilino]methyl]cyclohexane-1-carboxylic acid	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-1-morpholin-4-yl-3-[4-[3-(piperidin-4-ylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-3-[4-[3-[(1-ethylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-3-[4-(3-aminophenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0017	uM
4-[2-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0018	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]-1,3-benzothiazole-7-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0018	uM
4-[(5S,9R)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-7-[5-(2H-tetrazol-5-yl)-2-pyridinyl]-1,3,7-triazaspiro[4.4]nonan-9-yl]benzonitrile	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0018	uM
1-[(E)-3-[3-chloro-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-2-(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94603: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-2)	ic50	0.0020	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-ethylsulfonylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0020	uM
(E)-1-morpholin-4-yl-3-[4-(2-piperidin-4-yloxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0020	uM
(E)-1-morpholin-4-yl-3-[4-[3-(thian-4-yloxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0021	uM
6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]pyridine-3-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0025	uM
(E)-1-morpholin-4-yl-3-[4-[2-(pyridin-3-ylmethoxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0025	uM
(E)-1-morpholin-4-yl-3-[4-[2-(oxan-4-yloxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0025	uM
4-[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0030	uM
4-[(5S,9R)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-7-(quinoline-6-carbonyl)-1,3,7-triazaspiro[4.4]nonan-9-yl]benzonitrile	273491: Inhibition of LFA1-mediated adhesion of T cell to HUVEC	ic50	0.0030	uM
(2S)-2-[[5,7-dichloro-2-(4-chlorobenzoyl)-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-methylsulfonylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0030	uM
4-[[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]methyl]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0034	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]pyridine-4-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0036	uM
(E)-1-morpholin-4-yl-3-[4-[2-(pyridin-4-ylmethoxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0037	uM
(E)-1-morpholin-4-yl-3-[4-(3-piperidin-4-yloxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0039	uM
1-[(E)-3-[3-chloro-4-(2-methoxyphenyl)sulfanyl-2-(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94605: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-9)	ic50	0.0040	uM
1-[(E)-3-[2,3-dichloro-4-(1-methylindol-5-yl)sulfanylphenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94601: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (1-10)	ic50	0.0040	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]-1,3-benzoxazole-5-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0040	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-sulfamoylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0040	uM
(E)-3-[4-[3-(methylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0044	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]-1,3-benzothiazole-6-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0044	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]-1,3-benzoxazole-7-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0048	uM
1-[2-[2,3-dichloro-4-[2-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]cyclopropyl]phenyl]sulfanylphenyl]piperidine-3-carboxylic acid	99600: Ability to block the adherence of leukocyte function-associated antigen-1 (LFA-1) expressing JY-8 cells and intercellular adhesion molecule (ICAM-1) by 50% in absence of serum	ic50	0.0050	uM
1-[(E)-3-[4-(1-methylindol-5-yl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	91754: Inhibition of intercellular adhesion molecule-1 (ICAM-1) binding to recombinant LFA-1, range(5-5)	ic50	0.0050	uM
(E)-3-[3-chloro-4-(2-methoxyphenyl)sulfanyl-2-(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	94606: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (3-10)	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-2-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid	501388: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells by cell migration assay	ic50	0.0050	uM
2-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]-1,3-thiazole-5-carboxylic acid	478179: Inhibition of LFA1-mediated adhesion of human T cells to ICAM1-expressing HUVEC by fluorescence assay	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-2-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(1-propan-2-yltriazol-4-yl)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0050	uM
(E)-1-morpholin-4-yl-3-[4-[3-(oxan-4-ylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0054	uM
1-[(E)-3-[2,3-dichloro-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94605: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-9)	ic50	0.0060	uM
1-[(E)-3-[2,3-dichloro-4-(2-propan-2-ylphenyl)sulfanylphenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94607: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (3-18)	ic50	0.0060	uM

CTD chemical–gene interactions

70 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, increases expression	3
Tretinoin	increases expression, increases reaction	3
Simvastatin	decreases reaction, affects expression, increases expression, decreases expression, affects binding (+2 more)	3
perfluorooctanoic acid	decreases expression, increases expression	2
Nickel	increases expression, decreases reaction, affects expression	2
Tetrachlorodibenzodioxin	increases expression	2
GSK-J4	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tributyltin	increases expression	1
trichostatin A	affects expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases secretion	1
methylmercury II	increases expression	1
di-n-butylphosphoric acid	affects expression	1
arctigenin	decreases secretion	1
perfluorooctane sulfonic acid	decreases expression	1
cerivastatin	decreases reaction, increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects localization, decreases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
ginsenoside compound K	affects binding, decreases reaction, increases expression	1
ginsenoside Rh1	decreases reaction, increases expression, affects binding	1
perfluorohexanesulfonic acid	decreases expression	1

ChEMBL screening assays

146 unique, capped per target: 109 binding, 37 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017447	Binding	Inhibition of LFA1 expressed in human JY cells interaction with ICAM1-IG expressed in human HeLa cell monolayer after 45 mins by cell adhesion assay	Cucurbitacins, cell adhesion inhibitors from Conobea scoparioides. — J Nat Prod
CHEMBL5210089	Functional	Affinity Phenotypic Cellular interaction (ELISA (inhibition of staphylococcal enterotoxin B-induced production of IL2 in human PBMC cells)) EUB0000310b ITGAL	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8IS	Abcam HCT 116 ITGAL KO	Cancer cell line	Male
CVCL_B8XM	Abcam MCF-7 ITGAL KO	Cancer cell line	Female
CVCL_B9L2	Abcam A-549 ITGAL KO	Cancer cell line	Male
CVCL_E4AI	K-562 KL/4	Cancer cell line	Female

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis